NEUROTROPE BIOSCIENCES (NTRP
Improving the lives of patients with Cognitive and
Neurodevelopmental disorders
Safe Harbor Statement
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Certain statements in this presentation, particularly those pertaining to our strategy, constitute forwardlooking statements. Such statements are based upon the current beliefs and expectations of management and are subject to significant risks and uncertainties. Actual results may differ from those set forth in the forward-looking statements.
Any statements that are not statements of historical fact (including statements containing the words
“ believes, ” “ plans, ” “ anticipates, ” “ expects, ” “ estimates ” and similar expressions) should also be considered to be forward-looking statements. There are a number of important factors that could cause actual results or events to differ materially from those indicated by such forward-looking statements.
These factors are contained in Neurotrope Inc.
’s filings with the SEC, including Neurotrope’s Form 10-K for December 31, 2014 and Form S-1 filed on December 1, 2014.
We encourage all viewers of this presentation to review the aforementioned filings.
THESE MATERIALS DO NOT CONSTITUTE AN OFFER TO SELL, OR THE SOLICITATION OF ANY OFFER TO BUY,
ANY SECURITIES OF THE COMPANY OR ANY ENTITY WHATSOEVER. ANY SUCH OFFER MAY ONLY BE MADE BY
A PRIVATE PLACEMENT MEMORANDUM OR PROSPECTUS ISSUED BY THE COMPANY. ANY REPRESENTATION
TO THE CONTRARY BY ANY PARTY SHOULD BE IGNORED.
The full text of Neurotrope’s SEC filings can be found at the SEC ’ s website
(http://www.sec.gov)
Overview
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Bryostatin lead compound
Novel mechanism for treatment of cognitive and neurodevelopmental disorders
Protein Kinase C (PKC) activator enhancing memory and learning
Extensive safety data from approx. 1,500 patients from NCI trials
Active programs in Alzheimer’s disease, Fragile X Syndrome (FXS) and
Niemann-Pick Type C disease (NPC)
Successfully completed phase 2a Alzheimer’s disease safety trial
Proof of Concept phase 2b trial for Alzheimer’s disease approved by FDA
150 patients study in moderately severe to severe Alzheimer’s disease
Granted Orphan Drug Designation by FDA for FXS
Ongoing preclinical development for NPC.
History
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Neurotrope funded in 2013 ($23 million raised) to license the patent portfolio, from the Blanchette Rockefeller Neuroscience Institute (BRNI), for clinical development of Bryostatin
By date of NTRP funding, over $200 million invested in research & development by the National Cancer Institute (NCI) and BRNI
Technology involves activation and up regulation of PKC
Extensive publications in peer reviewed journals
Bryostatin used for Alzheimer’s disease treatment in FDA-approved
Compassionate Use cases
Phase 2a Alzheimer’s disease clinical trial completed in Q4 2014
Letter of intent signed with Worldwide Clinical Trials to commence
Phase 2b proof of concept trial Q2 2015
Received FDA Orphan Drug Designation for Fragile X syndrome Q1
2015.
Bryostatin – Lead Compound
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Bryostatin is derived from a marine organism, Bugula
Neritina
Bryostatin potent activator of PKC
Promotes synaptic function and synaptogenesis
Inhibits neuronal cell death
NCI has significant bryostatin supply and through BRNI has supplied NTRP
NTRP has sufficient amounts for upcoming Phase 2b trial
In conjunction with Stanford Univ. and Dr. Paul Wender, bryostatin is being synthesized for commercial use.
Scientific Rationale
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PKC is known to play a pivotal role in learning and memory
Bryostatin is a small molecule, penetrates blood-brain barrier and activates PKC which:
Increases brain-derived neurotropic factor (BDNF)
Improves synaptic function
Promotes new synapse formation
Matures immature synapses
Activates enzymes which alters amyloid metabolism and activates three degradation pathways
Activates Anti-apoptotic pathways
In NPC activation of PKC results in phosphorylation of a transport protein resulting in transport of lipids within and out of affected cells.
Alzheimer’s disease
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Preclinical work at BRNI demonstrated improved memory and learning in two different AD mouse models
Clinical Work
FDA approved several Compassionate Use protocols in severe AD patients
Three patients treated, current patient treated for approximately one year
Significant improvement in cognition and activities of daily living over treatment period
Phase 2a clinical trial completed
Bryostatin appeared safe and well tolerated
Demonstrated activation of PKC target
Phase 2b proof of concept trial – activities initiated.
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PKC and Alzheimer’s Disease
Mouse model demonstrating reduction of PKC in AD brain and increase of PKC following bryostatin treatment.
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Scientific Rationale (cont.)
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Brain Derived Neurotropic Factor
Treatment with bryostatin increases BDNF expression in AD transgenic mice.
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Improving Synaptic Function
Treatment with bryostatin increases total dendritic spine count in AD transgenic mice – Improving synaptic function.
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Synapse Formation
Treatment with bryostatin increases total synapses in AD transgenic mice.
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PKC Activation and Learning
Treatment with bryostatin improves memory and learning in Tg2576 AD transgenic mice.
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PKC Activation and Learning
Treatment with bryostatin improves memory and learning in 5X FAD transgenic mice.
Memory Learning
C+Vehicle C+Bry 100
80
60
40
20
0
1st Trial
Day
1 2 3
TG+Vehicle Tg+Bry
4 5 6
3
2
1
N
*
*
0
C+ Tg+ Tg+ C+
Phase 2b Clinical Trial Design
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150 moderately severe to severe AD patients
First patient enrolled planned for summer of 2015
Primary efficacy endpoint based on Severe Impairment Battery
Scale (SIB)
Secondary efficacy endpoints – Activities of Daily Living (ADL),
Neuropsychiatric Inventory (NPI) and MMSE
Three dosing levels of bryostatin vs. placebo
Initial dose three months then crossover for three months
First three month data targeted 2H 2016
Six month data targeted 1H 2017
World Wide Clinical Trials chosen as CRO
30 sites planned in U.S.
Orphan Drug Program – Fragile X
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Most common single gene cause of intellectual disability
Part of autism spectrum
~135,000 patients in U.S.
Preclinical cognitive studies performed at BRNI
Orphan Drug Designation granted Q1 2015
Clinical trial planned to begin Q4 2015.
Fragile X Mouse Model
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Treatment with bryostatin for 13 weeks beginning at two months
Biochemical and morphologic effects at the synaptic level that improves synaptic function, matures synapses and increases synapse formation - all resulting in improved cognition.
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Fragile X Mouse Model
Treatment with bryostatin in FX mouse results in restoration of synapses and improved memory & learning.
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Orphan Drug Program -
Niemann Pick Type C disease
NPC is a lysosomal storage disease affecting mostly children
Often causes death within the first two decades of life
Originates from a gene defect that results in the inability to transport lipids within and between cells
NTRP signed exclusive licensing agreement with Mt. Sinai School of
Medicine (NY) for the work of Dr. Yiannis Ioannou, an expert in NPC, for use of bryostatin in NPC
Dr. Ioannou has shown bryostatin can correct the lipid transport defect in
NPC cell lines
NTRP and Mt. Sinai currently investigating bryostatin in NPC mouse model
NTRP goal is to initiate human trials before the end of 2016 based on successful animal experiments.
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Timeline
Q1 2015
Phase 2a clinical trial AD safety study - COMPLETE
Orphan drug designation for Fragile X – GRANTED
Enroll additional Compassionate Use patients - ONGOING
Q2 2015
Initiation of Phase 2b Proof of Concept study for moderately severe to severe Alzheimer’s patients, FDA approves study
LOI with Worldwide Clinical Trials – SIGNED
Tripartite agreement for Fragile X with NTRP, FRAXA and U of
Santiago –SIGNED
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Timeline
Q3 2015
First patient enrolled in Phase 2b clinical trial
Develop clinical strategy for Fragile X with regulatory agency
Q4 2015
Fragile X Phase 2 PK and safety study initiated.
Scientific Collaborations
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Alzheimer’s Disease and Bryostatin
Blanchette Rockefeller Neuroscience Institute
Stanford University
Synthetic development of bryostatin
Bryolog development
Marinus Scientific
Harvesting and extraction of natural bryostatin
Clinical Advisory Board (slides follows)
Scientific Collaborations (cont.)
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Fragile X Syndrome
Blanchette Rockefeller Neuroscience Institute
Preclinical cognitive studies
FRAXA Research Foundation
University of Chile in Santiago/preclinical behavioral studies
Clinical Advisory Board
Rush University Medical Center-Chicago,
Seattle Children’s Hospital
Cincinnati Children’s Hospital Medical Center
Scientific Collaborations (cont.)
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Niemann-Pick Type C
Icahn School of Medicine at Mount Sinai (NYC)
Preclinical in-vitro and in-vivo studies
Albert Einstein School of Medicine (NYC)
Preclinical in-vivo studies, CNS pathology
Clinical Advisory Board
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Dr. Jeffrey L. Cummings, MD, ScD, CCF - Chairman
Director of Cleveland Clinic Lou Ruvo Center for Brain Health
Professor of Neurology and Psychiatry, Director of MSE Center for AD Research and Director of the
DFJ Center for Neurotherapeutics at UCLA
Expert in clinical trial design & analysis, global trial implementation, outcome measures
Authored or edited 30 books and published 600 peer-reviewed papers
Past President of Behavioral Neurology Society & American Neuropsych. Association.
Dr. Martin R. Farlow, MD
Professor and Vice Chairman of Research, Dept. of Neurology Indiana University
Associate Co-Director of the Indiana AD Center and member of gov’t. AD task force
Principal Investigator of the Indiana site of the AD Cooperative Study Unit
Published 200 peer-reviewed papers.
Dr. Samuel E. Gandy, MD, PhD
Mount Sinai Chair in AD Research, Professor of Neurology and Psychiatry at Mount Sinai
Director of the Mount Sinai Center for Cognitive Health and NFL Neurological Care
Former Chairman of the National Medical & Scientific Advisory Council of the AD Association
Founding Director of the Farber Institute of Neurosciences, Jefferson Medical College
Discovered PKC regulation of amyloid precursor phosphorylation and processing.
Clinical Advisory Board (cont.)
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Dr. Cristina Sampaio, MD, PhD
Chief Medical Officer at CHDI Foundation
Professor of Clinical Pharmacology and Therapeutics University of Lisbon,
Portugal
Former member of the Committee of Proprietary Medicinal Products and the
Scientific Advice Working Party at the European Medicines Agency.
Dr. Michael Weiner, MD
Professor UCSF School of Medicine in Radiology and Biomedical Imaging
Principle Investigator of the AD Neuroimaging Initiative
Educated at Mount Sinai and Yale, previously Assistant Professor of Medicine at
Stanford
Established the MR Unit at the San Francisco VA Medical Center.
Leadership Team
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Charles S. Ramat – President, Chief Executive Officer and Board member
Extensive operational and general business experience in both public and private companies
Industry focus - Biotechnology, medical devices, commercial finance, real estate
Paul Freiman – Chairman of the Board
Seasoned pharmaceutical executive
Former Chairman and CEO Syntex – Sold to Roche for $5 billion+
Board member NovaBay Pharmaceutical (NYSE: NBY)
Chairman Chronix BioMedical.
Leadership Team (cont.)
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Dr. Dan Alkon – Chief Scientific Officer
Graduate of Cornell Medical School
30 year career as Medical Director and Lab Chief in US NIH specializing in memory disorders
14 years as founding Scientific Director of BRNI
Dr. Warren W. Wasiewski – Chief Medical Officer
Board certified in Neurology and Pediatrics
Over 30 years of medical and pharmaceutical experience
Extensive clinical & regulatory experience in Neurology, Pediatrics and Orphan disease space at AstraZeneca, InfaCare and Alexion
Robert Weinstein, CPA, MBA – Chief Financial Officer
Experienced healthcare industry CFO and consultant
Successful healthcare private equity fund manager & investment banker.
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Trading and Capitalization
Ticker symbol
Current share price (5/19/15)
Capital raised during 2013
Cash as of May14, 2015
Trading
Current Capitalization
Common Stock
Series A Convertible Preferred Stock (Convertible @ $1.00 / share)
Options & Warrants Outstanding (Weighted Avg. E.P. $1.39 / share)
Total fully diluted shares
Information
NTRP
$0.96
$23 million
$4.5 million
Shares
27.6 MM
18.0 MM
9.0 MM
54.6 MM
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